Further validation and psychometric properties of the Spanish adaptation of the Genetic Counseling Outcome Scale.

Evaluation of clinical genetic services is challenging due to the nature of their interventions. The Genetic Counseling Outcome Scale (GCOS-24), a patient-reported outcome measure, was developed to measure empowerment, an important patient-reported outcome from genetic counseling. Previously, we translated and adapted GCOS-24 for use in Spain, but neither test-retest reliability nor structural and construct validity were assessed at that time. In the present study, we set out to test the reliability and validity of the Spanish adaptation of the GCOS-24 against already validated Spanish language measures of satisfaction with life, anxiety, and health locus of control. 880 patients/families who attended the genetics clinic were invited to participate in a online survey. 201 participants (23%) completed the four questionnaires at the first timepoint, and 59 of these (29%) completed GCOS-24 again the second timepoint, 2-4 weeks later. Test-retest reliability was confirmed, with no significant differences between responses to GCOS-24 at the first and second timepoints and good internal consistency. Convergent validity was confirmed between GCOS-24 and measures of satisfaction with life and anxiety but not with measures of health locus of control. For the structural and construct validation, an exploratory factor analysis was performed. The resulting factorial structure of GCOS-24 consists of 6 factors that accumulate 68% of the variance shared by the 21 items that remained in the model. We applied the factor structure of the three validated measures to the available data and analyzed the correlation between factors of GCOS-24 and the other scales. The results showed significant and consistent correlation with factors of the satisfaction with life and anxiety scales but no significant correlation with internal health locus of control. The use of the Spanish adaptation of GCOS-24 in other genetic clinics in Spain will help to validate it further. This study contributes to the international validation of GCOS-24 to evaluate the quality of genetic counseling in Europe.

Characterization of a 8q21.11 microdeletion syndrome associated with intellectual disability and a recognizable phenotype.

We report eight unrelated individuals with intellectual disability and overlapping submicroscopic deletions of 8q21.11 (0.66-13.55 Mb in size). The deletion was familial in one and simplex in seven individuals. The phenotype was remarkably similar and consisted of a round face with full cheeks, a high forehead, ptosis, cornea opacities, an underdeveloped alae, a short philtrum, a cupid's bow of the upper lip, down-turned corners of the mouth, micrognathia, low-set and prominent ears, and mild finger and toe anomalies (camptodactyly, syndactyly, and broadening of the first rays). Intellectual disability, hypotonia, decreased balance, sensorineural hearing loss, and unusual behavior were frequently observed. A high-resolution oligonucleotide array showed different proximal and distal breakpoints in all of the individuals. Sequencing studies in three of the individuals revealed that proximal and distal breakpoints were located in unique sequences with no apparent homology. The smallest region of overlap was a 539.7 kb interval encompassing three genes: a Zinc Finger Homeobox 4 (ZFHX4), one microRNA of unknown function, and one nonfunctional pseudogen. ZFHX4 encodes a transcription factor expressed in the adult human brain, skeletal muscle, and liver. It has been suggested as a candidate gene for congenital bilateral isolated ptosis. Our results suggest that the 8q21.11 submicroscopic deletion represents a clinically recognizable entity and that a haploinsufficient gene or genes within the minimal deletion region could underlie this syndrome.